The role of small RNAs in epigenetic regulation is an emerging field. This research may also open novel treatment strategies based on manipulation of the epigenetic status of the target tissues. Our objective is to review epigenetic regulation of key vascular genes and growth factors. Vascular endothelial growth factor A (VEGF-A) is one of the key players in regulating and maintaining cardiovascular functions and pathology. Although its epigenetic regulation is still not completely understood, expression of the VEGF gene can be manipulated by epigenetic mechanisms using small RNAs that are targeted to the gene promoter which results in the alteration of histone code. VEGF exerts its effects mostly through two receptors, VEGFR1 and VEGFR2, and their expression is also regulated by promoter DNA methylation in various cancer cells. These findings suggest the importance of epigenetic mechanisms in the regulation of vascular functions.